RU2166335C1 - Method of dialyzing solution preparing - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: invention relates to detoxification by dialysis methods. Preparing dialyzing solution involves addition of components of dialyzing solution to purified water. In purified water pH value is increased by electrochemical treatment to value 8.0-11.0. Then before addition of solution components water is treated in anode chamber of diaphragm electrochemical reactor up to pH value 6.9-7.5 and oxidative-reductive potential value +400 - +1000 mV relative to chlorosilver comparator electrode. Before pH value increase sodium chloride at concentration 0.5 g/l, not above, is added to the purified water. EFFECT: enhanced bactericidal and absorption activity, increased buffer capacity of dialyzing solutions. 11 cl, 6 tbl, 4 dwg, 4 ex _

Description

 The invention relates to medicine and can be used for purification and treatment of biological fluids by dialysis methods, including extracorporeal ones.

 Currently, dialysis methods of purification of biological fluids of the human body are widely used in medicine to remove endogenous and exogenous toxins from the body. Among the factors ensuring the success of extracorporeal detoxification, an important role belongs to the dialysis solution. The composition of dialysis solutions is selected depending on the humoral disorders in the patient. The concentration in these solutions of magnesium (0 - 1 meq / l) and potassium (0 - 4 meq / l) is selected individually, the introduction of sodium (140 meq / l) and calcium (4.5 meq / l) corresponds to their physiological concentration in plasma and the concentration of chlorine in the dialysis solution is higher than the physiological norm (up to 117 meq / l), the glucose concentration is usually 200 mg%. The solution may also contain buffers, such as acetate or sodium bicarbonate [1]. Despite a slight difference in the composition of the various prescriptions of dialysis solutions, they are all prepared according to the same procedure.

 The method of obtaining dialysis solutions used in medicine includes preliminary purification of water, introducing calculated quantities of solution components into it, for example, by mixing purified water and an aqueous solution of a concentrate [2].

 A disadvantage of the known solution is that the resulting solutions can be adjusted only by the quantitative composition of the components and all of them have limited absorption activity. In addition, there is a high probability of bacterial contamination of the solution in contact with the environment. It should also be noted that the known methods for preparing a solution give a solution with a small buffer capacity, which can contribute to a change in metabolic processes in humoral media during dialysis. Solutions obtained in a known manner require that the increased integrity requirements of the dialysis membranes be observed, since even small amounts of the dialysis solution get into the bloodstream of the body there is a high probability of injury to these pathways.

 The technical result of the application of the present invention is the possibility of obtaining dialysis solutions having increased bactericidal activity, increased buffer capacity and increased absorption activity, as well as solutions having an increased affinity for cleaned biological fluids and reducing the likelihood of injury when small amounts of such a solution enter the bloodstream of the body .

 This result is achieved in that the method of obtaining a dialysis solution includes pre-treatment of water and mixing purified water with an aqueous concentrate, which includes components of the dialysis solution, such as sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glucose, acetate or sodium bicarbonate, as well as additional operations for the treatment of already purified water, carried out before mixing. So, in purified water, the pH value is increased to a value of 8–11, and then it is processed in the anode chamber of the diaphragm electrochemical reactor to achieve pH values of 6.9–7.5 and the redox potential of +400 ... +1000 mV relative to the silver chloride reference electrode .

 In the case of using distilled or close in composition water, sodium chloride is introduced into the purified water before the pH is increased, the concentration of which does not exceed 0.5 g / l.

 If, when treating purified water or purified water with chloride introduced in the anode chamber, pH values lower than 6.9 or higher than 7.5 are obtained, then the dialysis solution prepared on such water cannot be used, since it has pH values different from pH values, body fluids. When the values of the redox potential, less than + 400 mV, relative to the silver chloride reference electrode, the resulting solution does not have the necessary disinfecting ability. With values of the redox potential greater than 1000 mV, the resulting solution has a high content of oxidizing agents, which can adversely affect the dialysis process. Preliminary pH adjustment within the specified limits allows not only to obtain the required pH value of the dialysis solution, but also to increase the buffer capacity of the resulting solution. With a preliminary change in pH below 8 as a result of subsequent electrochemical treatment, it is not possible to obtain a solution having the required bactericidal activity and buffer capacity, and with a preliminary pH adjustment to values greater than 11, subsequent electrochemical treatment leads to an excessive amount of oxidizing agents in the solution, which negatively affects the dialysis process .

 In addition, electrochemical treatment allows to increase the absorption capacity of the solution.

 In medical practice, it is known to use electrochemically treated solutions containing 0.89% concentration of sodium chloride to accelerate the detoxification of the body, by reinfusion of such a solution [3].

 However, in the known method, the electrochemical treatment is performed in a diaphragm-free electrochemical reactor, which leads to the formation of mainly sodium hypochlorite. In addition, in the known solution, the biological fluids and the solution processed in the electrochemical reactor are mixed in a ratio of 1: 1, which limits the possibilities of using the known solution.

 In the proposed solution, the processing is carried out in the anode chamber of the diaphragm electrochemical reactor and the resulting solution is not infused, but is used as the aqueous component of the dialysis solution in dialysis methods of detoxification of the body. In addition, it should be noted that this treatment in the anode chamber increases the bactericidal properties of the solution and the dialysis solution obtained on this basis can be used to disinfect biological body fluids, and in particular donor blood.

 Preliminary adjustment of pH values in purified water or in purified water with sodium chloride introduced can be carried out using reagents, however, in this case, it is necessary to strictly monitor the qualitative and quantitative composition of the reagents, avoiding the violation of the formulation of dialysis solutions. Therefore, it is preferable to carry out preliminary pH adjustment by treating the water in the cathode chamber of a diaphragm electrochemical reactor and then supplying it to a flotation reactor, in which at least part of the treated water is separated together with hydrogen gas before treatment in the anode chamber of the same reactor. The amount of solution discharged into the drain is determined by the pH value and can reach 40% of the total amount at pH 11.

It is also possible to preliminary increase the pH in purified water or in purified water with sodium chloride introduced into it by treating the water sequentially in the cathode and anode chambers of the main diaphragm electrochemical reactor, with a specific electricity consumption of 20 - 2000 C / l. After that, the solution is fed into the anode chamber of an additional electrochemical reactor, where they conduct anode processing until the pH reaches 6.9 - 7.5 and the redox potential +400 ... + 900 mV relative to the silver chloride reference electrode. The cathode chamber of the additional electrochemical reactor is equipped with a secondary auxiliary electrolyte circulation circuit with a capacity, moreover, the pH of the auxiliary electrolyte circulating in the cathode chamber is maintained at a level of at least 10 and processing in the additional electrochemical reactor is carried out when the pressure in the anode chamber is 0.1 times higher than in the cathode - 0.4 kgf / cm ² .

Processing in an additional electrochemical reactor when the pressure in the anode chamber is higher than 0.1 to 0.4 kgf / cm ² compared to the cathode one allows to negate the negative effects of ion electromigration in the additional reactor and to purposefully change the properties of the resulting solution. At a pressure of less than 0.1 kgf / cm ^{2, the} migration of ions from the cathode chamber to the anode cannot be suppressed, and an excess of pressure above 0.4 kgf / cm ² does not lead to a new result but increases the cost of the process.

 Processing the auxiliary electrolyte in the cathode chamber in a circulating mode provides the opportunity to reduce the discharge of electrolyte into the drainage and stabilize the operation of the additional reactor by maintaining the constant characteristics of the auxiliary electrolyte. The pH value of the electrolyte in the circulation circuit is maintained at a level of at least 10. Lowering the pH below 10 does not allow to obtain a dialysis solution with the desired characteristics. The pH values are adjusted by changing the concentration of the electrolyte solution by removing part of the treated electrolyte from the circuit to the discharge and replenishing the circuit with fresh electrolyte.

 As an auxiliary electrolyte, purified water is used with sodium chloride introduced into it, and the neutral anolyte is withdrawn from the anode chamber of the additional electrochemical reactor through a pressure regulator.

 Purified water is also used as an auxiliary electrolyte, at least a portion of gaseous and dissolved hydrogen is removed from it before the treated water is supplied to the anode chamber of the first electrochemical reactor, and neutral anolyte is removed from the anode chamber of the additional electrochemical reactor through a pressure regulator.

 Or, purified water is used as an auxiliary electrolyte, at least a part of free and dissolved electrolysis gases is removed from it before the treated water is supplied to the anode chamber of the additional electrochemical reactor, and neutral anolyte is removed from the anode chamber of the additional reactor through a pressure regulator.

 The use of purified water as an auxiliary electric stove allows avoiding changes in the composition of the dialysis solution due to the electromigration of ions through the diaphragms of electrochemical cells during processing.

 When processing it is advisable to use electrochemical reactors with ultrafiltration or nanofiltration diaphragms made of ceramics, for example, ceramics based on zirconium oxide.

 The zirconia ceramic diaphragm may also contain additives of aluminum and yttrium oxides, or a zirconia ceramic diaphragm with additives of aluminum and yttrium oxides is used.

 Ceramic diaphragms do not change their characteristics during differential pressure and during processing, which ensures the stability of processing parameters.

 The composition of ceramics is selected based on the conditions of the problem being solved, but it should be noted that ceramics based on zirconium oxide or ceramics based on zirconium oxide with the addition of aluminum and yttrium oxides have an optimal combination of characteristics to solve the problems posed.

 When implementing the method, both the preparation of the solution and the regulation of pH in purified water or in purified water with sodium chloride introduced into it is advisable to use flowing electrochemical reactors described in RF patent N 2078737 or US patent N 5635040. These reactors are compact diaphragm electrolyzers, made of vertical cylindrical and rod electrodes coaxially mounted in dielectric bushings, a ceramic diaphragm also coaxially mounted in bushings between the ele trodes and dividing the interelectrode space, the electrode chamber, wherein the chambers have inlet in the bottom and out the top part of the cell. The electrolyzers are made on a modular basis, which allows you to implement a method with a given performance.

 Adjusting the pH of the purified water or purified water with the introduction of sodium chloride if necessary and subsequent anode treatment is carried out using plants, the schemes of which are presented in FIG. 1-4. Treated water is then used to prepare the dialysis solution.

 The pH control unit (Fig. 1) consists of the main diaphragm flow-through electrochemical reactor 1, which is either a single diaphragm flow-through electrochemical module or a block of these elements connected hydraulically in parallel; a water-jet pump 2, an adjustable valve 3, a purified water supply line 4, a sodium chloride solution supply line 5, a treated water drainage line 6, a flow line 7 from the cathode chamber of the main reactor 1 to its anode chamber and flotation reactor 8 with a line for the removal of part of the treated water and control valve 9, which is installed on line 7.

 Installation works as follows.

 Purified water through line 4 is supplied to the cathode chamber of reactor 1 by means of a water-jet pump. If necessary, sodium chloride solution enters the water-jet pump through line 5 to be mixed with purified water for dialysis. The amount of chloride solution is regulated by valve 3. After cathodic treatment, a stream having a pH of 8-11 enters flotation reactor 8. In flotation reactor 8, a part of catholyte is separated together with hydrogen gas and these products are discharged into drainage through adjustable valve 9, and then anodic treatment of the catholyte stream remaining after these operations in the anode chamber of reactor 1 until the pH values of 6.9 - 7.5 and the values of the redox potential + 400 ... + 1000 mV are reached.

 Installation for regulating the pH of purified water can be performed with the main and additional reactors (Fig. 2-4). In this case, it consists of the main 1 (Fig. 2) and additional 2 diaphragm flow-through electrochemical reactors, which are either a single diaphragm flow-through electrochemical module or a block of these elements connected hydraulically in parallel; auxiliary electrolyte 3 tanks, water-jet pump 4, adjustable valve 5, purified water supply line 6, sodium chloride solution supply line 7, mixer 8, pressure regulator 9, auxiliary electrolyte removal line 10, treated water removal line 11. The installation also contains line 12 the overflow from the cathode chamber of the main reactor 1 to its anode chamber and the overflow line 13 from the anode chamber of the main reactor 1 to the anode chamber of the secondary reactor 2. In addition, the installation may include a separator for separating liquid teeing off gas 14, which may be mounted on line 12 (FIG. 3) or on the line 13 (FIG. 4).

 Installation works as follows.

 The sodium chloride solution along line 7 with the help of pump 4 enters the mixer 8, in which it is mixed with purified water (if necessary, with pump 4 turned on), coming through line 6 (Fig. 1). The solution obtained in the mixer is fed into the cathode chamber of the main reactor 1 and also through the control valve 5 fills the circulation circuit and the capacity 3 of the additional reactor 2.

 From the cathode chamber of the main reactor 1, the solution through line 12 enters the anode chamber of the reactor 1, and after exiting it, a solution having a pH of 8.0 - 11.0 is supplied through line 13 to the anode chamber of the additional reactor 2 and after processing in this chamber and achieving the required parameters through line 11 through the pressure regulator 9, the treated water is supplied to prepare a dialysis solution.

 In the process of processing the solution in the main reactor during flow from the cathode chamber to the anode on line 12, a separator 14 can be installed to separate the liquid and gas (Fig. 2). As a result, a solution is supplied to the anode chamber only with dissolved gases, but without gas bubbles, which allows changing the chemical composition of the treated water (increasing the yield of ozone and peroxide compounds).

 If the separator 14 is placed on line 13 (Fig. 3) then the biocidal substances of the obtained water are mainly represented by oxygen compounds of chlorine.

 The invention is illustrated by the following examples, which, however, do not exhaust all possible embodiments of the proposed method.

 In all examples, an electrochemical reactor according to RF patent N 2078737 was used with coaxially mounted cylindrical and rod electrodes and a ceramic ultrafiltration diaphragm made of ceramic coaxially mounted between them based on a mixture of zirconium, aluminum and yttrium oxides (60, 37 and 3 wt.%, Respectively) and 0.7 mm thick. The electrodes used were titanium coated from a mixture of ruthenium and iridium oxides (anode) and titanium with a pyrocarbon coating (cathode). The cell length was 200 mm, and the volumes of the electrode chambers were 10 ml of the cathode chamber and 7 ml of the anode chamber.

Example 1. In the water purified for hemodialysis, a solution of sodium chloride is introduced to a concentration of the latter of 0.3 g / L. The resulting solution is treated in the apparatus shown in FIG. 1, until a pH of 9.5 is reached after treatment in a cathode chamber. After separation of a 20% volumetric flow in a flotation reactor together with hydrogen gas, the flow is treated in the anode chamber until a pH of 7.2 and a redox potential of + 850 mV relative to the silver chloride reference electrode is reached. In the treated solution, the concentrate of the components of the dialysing solution, respectively, of the prescription A1 was dissolved in the ratio of the concentrate - solution 1:35. The sodium concentration in the resulting solution did not exceed 140 meq / l. In the resulting solution, the pH of the dialysis solution was determined by the Astrup method [4], alkaline reserve by the Johnson method [4], and the volumetric content of CO _{2 was} also determined by the Johnson method [4]. Comparative measurements were carried out with dialysis solution A1 of the laboratory of Soludia (France), prepared in a known manner by dissolving a concentrate in demineralized water with a dilution ratio of 1:35. The data are presented in table 1.

 Example 2. In the water purified for hemodialysis, a sodium chloride solution is introduced to a concentration of the latter of 0.1 g / L. The resulting solution is treated in the apparatus shown in FIG. 2, until pH 8 is reached after treatment in the cathode and anode chambers of the main reactor, followed by feeding an additional reactor into the anode chamber and processing in it until pH 7 and a redox potential of + 500 mV with respect to the silver chloride reference electrode are reached. In the treated solution, the concentrate of the components of the dialysing solution, respectively, of the prescription A1 was dissolved in the ratio of concentrate - solution 1:35. The resulting solution was used for bench hemodialysis of donated blood. In the blood, before hemodialysis and after, the creatinine content was determined by the Popper method [5], urea urease with phenol-hypochlorite [5], the content of potassium and sodium ions by flame photometry [5], and blood toxicity by the paramecium test (survival time of paramecium) . Comparative measurements were carried out on bench hemodialysis of the same donated blood using dialysis solution A1 of the laboratory of Soludia (France), prepared in a known manner - by dissolving the concentrate in demineralized water with a dilution ratio of 1:35. The data are presented in table 2.

 Example 3. In the water purified for hemodialysis, a sodium chloride solution is introduced to a concentration of the latter of 0.5 g / L. The resulting solution is treated in the apparatus shown in FIG. 2, until reaching pH values of 7.1 and a redox potential of + 700 mV relative to the silver chloride reference electrode. In the treated solution, the concentrate of the components of the dialysis solution, respectively, of the prescription A1 was dissolved in the ratio of the concentrate - solution 1:35. The resulting solution, having a pH of 7.88 and a value of the redox potential of 595 mV, was used for bench hemodialysis of donated blood. Chilean blood of 4.4 l / min was processed at the stand as a model medium in the dialysis circuit recirculation mode with a volumetric flow of 180 ml / min. Comparative tests were performed with a dialysis solution based on Dial Medical Supply bicarbonate concentrate (pH = 7.85; ORP = 380 mV).

The model medium was seeded in experiment 1) with dichloroethane [DCE] (650 mg / 4.4 L); in experiment 2) carbon tetrachloride [CCl ₄ ] (50 mg / 4.4 L). The etched model medium was poured into the dialysis circuit and processed in the prototype of the DIP-2 dialyzer (the area of the dialysis membrane was 0.8 m ² ). Dialysis was carried out using the dialysis solution of the prototype (series A) and using the dialysis solution obtained in accordance with the invention (series B). Perfusion volume = 3 • BCC.

The content of dichloroethane and CCl ₄ in the model fluid was determined by gas-liquid chromatography. In parallel, pH and ORP measurements of the model medium were performed. The dynamics of changes in the parameters of the model medium inoculated with DCE and CCl ₄ during detoxification by hemodialysis (bench test) are presented in tables 3 (series A) and 4 (series B).

The presented data show that the purification of blood from the seed of DCE and CCl ₄ by dialysis and using a dialysis solution of the prototype ensures the removal of these hydrophobic toxins by 25-30% with a perfusion volume of 3 • BCC. The use of the dialysis solution according to the invention removes 84 to 85% of hydrophobic toxins in the same dialysis mode in a bench test. In addition, the removal of toxic concentrations of DCE and carbon tetrachloride from the blood is accompanied by a normalization of pH and a shift in blood ORP towards recovery values.

 Example 4. In the conditions of example 3, we determined the indicators for removing from the volume of circulating blood various biochemical components during dialysis using a dialysis solution according to the prototype (series A) and according to the invention (series B). The experimental results are presented in tables 5 (series A) and 6 (series B).

 As follows from the presented data, the use of the dialysate solution according to the invention accelerates the removal of metabolic slag (urea, bilirubin) from the bcc, maintains the overall level of potassium and protein, improves the effect of pH correction with a shift in the ORP towards the recovery values.

 As follows from the above data, the solutions prepared in accordance with the proposed invention have increased bactericidal activity, increased buffer capacity and increased absorption activity. Solutions also have an increased affinity for cleaned biological fluids and reduce the likelihood of injury when small amounts of such a solution enter the body’s bloodstream and can be effectively used to remove toxic products from the humoral environment of the body (blood, lymph) using the dialysis method used to detoxify various pathological conditions.

Sources of information
1. Big Medical Encyclopedia, Moscow: Soviet Encyclopedia, 1977, p. 166.

 2. N. A. Lopatkin, Yu.M. Lopukhin. Efferent methods in medicine. - M .: Medicine, 1989, p. 255 (prototype).

 3. USSR author's certificate N 1194425, A 61 M 1/38, 1985.

 4. Zernov N.G., Yurkov Yu.A. Biochemical studies in pediatrics. - M.: Medicine, 1969, pp. 149-152.

 5. Menshikov VV Laboratory research methods in the clinic (reference). - M.: Medicine, 1987, pp. 217-221, 261-262.

Claims (11)

 1. A method of obtaining a dialysis solution, comprising introducing into the water purified for dialysis dialysis solution components and mixing, characterized in that the purified water before displacement is subjected to additional processing by first raising the pH of the purified water to a value of 8-11 with subsequent processing of water in the anode chamber a diaphragm electrochemical reactor, moreover, water is treated in the anode chamber until a pH of 6.9 - 7.5 and an oxidation-reduction potential of +400 ... +1000 mV are reached relative to silver chloride reference electrode.  2. The method of obtaining the dialysis solution according to claim 1, characterized in that the components of the dialysis solution are sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glucose, acetate or sodium bicarbonate in dry form or in the form of an aqueous concentrate.  3. The method of obtaining the dialysis solution according to claim 1, characterized in that before increasing the pH, sodium chloride is introduced into the purified water to a concentration not exceeding 0.5 g / l.  4. A method of obtaining a dialysis solution according to claims 1 to 3, characterized in that the additional treatment of purified water or purified water with sodium chloride introduced into it is carried out using one diaphragm electrochemical reactor, and a preliminary increase in the pH value in water to 8-11 is carried out treatment in a cathode chamber of a diaphragm electrochemical reactor, followed by feeding into a flotation reactor, in which at least a portion of the treated water is separated together with hydrogen gas, and the subsequent anode th processing water until reaching pH of 6.9 - 7.5 and a redox potential of 400 ... 1000 mV vs. silver chloride reference electrode in the anode chamber are the same reactor. 5. A method of obtaining a dialysis solution according to claims 1 to 3, characterized in that the additional treatment of purified water or purified water with sodium chloride introduced into it is carried out using the main and additional diaphragm electrochemical reactors and a preliminary increase in pH in purified water or in purified water with sodium chloride introduced into it up to 8 - 11, water is treated sequentially in the cathode and anode chambers of the main diaphragm electrochemical reactor with a specific electricity consumption of 20 - 2000 C / l, with the subsequent supply of water to the anode chamber of the additional reactor, the water is treated in the anode chamber of the additional reactor until pH values of 6.9 - 7.5 and the redox potential of +400 ... +900 mV relative to the silver chloride reference electrode are reached, the treated water is removed from the anode chamber of the additional reactor and serves at the stage of preparation of the solution, and in the cathode chamber of the additional reactor process the auxiliary electrolyte, while the cathode chamber of the additional electrochemical reaction the torus is equipped with a circulation circuit with a capacity and pH of the auxiliary electrolyte circulating in the cathode chamber, maintained at a level of at least 10, and the treatment of water and auxiliary electrolyte in the additional electrochemical reactor is carried out when the pressure in the anode chamber is 0.1-0 higher than the cathode 4 kgf / cm ² .  6. The method of producing the dialysis solution according to claim 5, characterized in that purified water with sodium chloride introduced into it is used as an auxiliary electrolyte, and the treated water or treated water with sodium chloride introduced into it from the anode chamber of the additional electrochemical reactor is withdrawn through pressure regulator.  7. The method of obtaining the dialysis solution according to claim 5, characterized in that purified water is used as an auxiliary electrolyte, at least a part of the gaseous and dissolved hydrogen is removed from it before the treated water is supplied to the anode chamber of the main electrochemical reactor, and the output of the treated water or treated water with sodium chloride introduced into it from the anode chamber of an additional electrochemical reactor is carried out through a pressure regulator.  8. The method of obtaining the dialysis solution according to claim 5, characterized in that purified water is used as an auxiliary electrolyte, at least a part of the free and dissolved electrolysis gases and the output of treated water are removed from it before supplying the treated water to the anode chamber of the additional electrochemical reactor treated water with sodium chloride introduced into it from the anode chamber of the additional reactor is carried out through a pressure regulator.  9. A method of obtaining a dialysis solution according to claims 1 to 8, characterized in that during the additional treatment of water, electrochemical reactors with an ultrafiltration or nanofiltration diaphragm made of ceramic are used.  10. The method of obtaining the dialysate solution according to claim 9, characterized in that during the additional treatment of water, electrochemical reactors with a diaphragm made of zirconia-based ceramic are used.  11. The method of obtaining the dialysate solution according to claim 9, characterized in that during the additional treatment of water, electrochemical reactors with a diaphragm made of zirconia-based ceramic with additions of aluminum and yttrium oxides are used.

Images